In previous work, we have shown that physical dependence does not develop during the state of hibernation in ground squirrels; it does develop in the usual fashion, however, in these animals while in the nonhibernating (i.e., euthermic) state. The experiments described in this proposal are designed to test the hypothesis that changes occur during hibernation in the functional parameters of the CNS endogenous opioid system that are responsible for the absence of morphine physical dependence. The specific aims ar thus to: a) determine the effect of low body temperature (assoicated with hibernation) on the development of morphine physical dependence, b) compare the intracerebral distribution pattern of intracerebroventricularly administered morphine in hibernating and euthermic brain, c) compare the binding characteristics (affinity, number of sites) of different types of opiate receptor in hibernating and euthermic brain, d) compare the regional concentration of opioid peptides (endorphins and enkephalins) in hibernating and euthermic brain, and e) determine the effects of opioid peptides (endorphins and enkephalins) on the control of the hibernating state and on the control of body temperature in hibernation and euthermic. These experiments will employ several techniques, including receptor binding, radioimmunoassay, single unit recording (and iontophoresis) of hypothalamic temperture-sensitive neurons and intracerebral microinjection of opioid peptides and antagonists (naloxone) in unanesthetized and unrestrained hibernating and euthermic animals. The long-term objectives of this project are to describe the CNS correlates of opioid physical dependence and the physiological role of opioid peptides in the CNS.